This is a revised, and greatly streamlined, proposal to investigate the role that iron may play in the cariogenic ability of Streptococcus mutans. The premise, as before, is that irons plays a role in pathogenesis of caries. The hypothesis is based on the large literature for other bacterial pathogens which contains, in some cases, elaborate mechanisms for the acquisition of iron. Furthermore, it is known that iron acquisition is directly tied in with established virulence mechanisms. In the revision, the author will pursue the argument that iron plays a role in the etiology of dental caries by establishing the following: mechanisms by which S. mutans acquires iron; identification of iron-responsive proteins in S. mutans; and the cloning and characterization of iron responsive gene(s) in the organism. Future experiments will hold forth on the previous aims concerning mutagenesis of iron responsive genes and rat caries experiments to verify the role of the genes in cariogenesis; and, finally RNA and gene fusion experiments to determine whether iron responsive genes are transcriptionally regulated.